Progress on this trans-institutional collaborative effort has focused on advanced quantitative morphometric analysis in the brains of behaviorally characterized subjects in relation to estrogen status. In a recent report currently under revision, for example, Hara et al. tested the possibility that the NMDA receptor distribution of phospho-Tyr1472-GluN2B (pGluN2B) in the prefrontal cortex i.e., the predominant form of GluN2B at the synapse - is sensitive to aging or estradiol treatment and coupled to working memory capacity. Experiments were conducted in ovariectomized young and aged subjects that received long-term cyclic vehicle or estradiol (E) treatment and were tested on the delayed response (DR) test of working memory. Subsequent serial section electron microscopic immunocytochemistry quantitatively assessed the subcellular distribution of pGluN2B. E treatment was associated with a variety of age-dependent effects, including an apparent redistribution of pGluN2B to the cytoplasm in older subjects. This effect positively correlated DR performance among aged animals, whereas the synaptic representation of pGluN2b inversely correlated working memory. Together, these findings prompt speculation that the reported benefits of cyclic E on prefrontal cortex function in aging arise partly from regulating NMDA receptor subunit composition at the synapse protective against excitotoxic damage.